Cancer cells compete for space and resources but also cooperate for the production of diffusible growth factors. The first objective of the project is to analyse the dynamics of the production of growth factors using theoretical models of non-linear public goods games in the framework of evolutionary game theory. The second objective is to test the predictions of the models using experiments with cancer cells in vitro. The overall goal of the project is to describe the dynamics and understand the ultimate causes of intra-tumor heterogeneity and of the evolution of resistance to therapies.

A description of the work performed since the beginning of the project:

I developed theoretical models of growth factor production in well-mixed populations of cancer cells (to simulate the dynamics of liquid tumors), in monolayers of cells (to simulate the dynamics in vitro) and in tridimensional tumors (to simulate the dynamics in vivo). I used genetically engineered cell lines to test the predictions of the theory in vitro by measuring how the frequency of different cell lines and their growth rates change over time and under different conditions.

A description of the main results achieved so far:

The results of the theoretical models show that under certain parameters cells producing growth factor will coexist with cells that do not produce growth factors, whereas in other cases producer cells will go extinct, leading to a reduction in the growth rate of the tumor. These predictions were verified using experiments with cancer cells in vitro.

The expected final results and their potential impact and use:

This work will shed light into the maintenance of intra-tumor heterogeneity, a feature that has long puzzled cancer biologists. The results also help understand why therapies that target growth factors lead to a temporary reduction in tumor growth followed by relapse, and may help devise evolutionarily stable therapies.